BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To ...BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer.In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.METHODS Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)database.Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases.Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients.The correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also analyzed.Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)genes.The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was performed.The study also validated the level of mRNA or protein expression of PDHB in several cancers.Finally,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver cancer.RESULTS PDHB was significantly and differently expressed in most cancers.PDHB was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinoma,and brain lower grade glioma.In some cancers,PDHB expression was clearly associated with gene mutations,clinicopathological stages,and expression of TMB,MSI,and ICP genes.The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment.In addition,single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells.This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation,migration,and invasion functions of hepatoma cells.CONCLUSION As a member of pan-cancer,PDHB may be a novel cancer marker with potential value in diagnosing cancer,predicting prognosis,and in targeted therapy.展开更多
BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AI...BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.展开更多
In this editorial we comment on the article by Tang et al published in the recent issue of World Journal of Hepatology.Drug therapy of intrahepatic cholangiocarcinoma(iCCA)poses an enormous challenge since only a smal...In this editorial we comment on the article by Tang et al published in the recent issue of World Journal of Hepatology.Drug therapy of intrahepatic cholangiocarcinoma(iCCA)poses an enormous challenge since only a small proportion of patients demonstrate beneficial responses to therapeutic agents.Thus,there has been a sustained search for novel molecular targets for iCCA.The study by Tang et al evaluated the role of 26S proteasome non-ATPase regulatory subunit 6(PSMD6),a 19S regulatory subunit of the proteasome,in human iCCA cells and specimens.The authors employed clustered regularly interspaced short palindromic repeat(CRISPR)knockout screening technology integrated with the computational CERES algorithm,and analyzed the human protein atlas(THPA)database and tissue microarrays.The results show that PSMD6 is a gene essential for the proliferation of 17 iCCA cell lines,and PSMD6 protein was overexpressed in iCCA tissues without a significant correlation with the clinicopathological parameters.The authors conclude that PSMD6 may play a promoting role in iCCA.The major limitations and defects of this study are the lack of detailed information of CRISPR knockout screening,in vivo experiments,and a discussion of plausible mechanistic cues,which,therefore,dampen the significance of the results.Further studies are required to verify PSMD6 as a molecular target for developing novel therapeutics for iCCA.In addition,the editorial article summarizes the latest advances in molecular targeted drugs and recently emerging immunotherapy in the clinical management of iCCA,development of proteasome inhibitors for cancer therapy,and advantages of CRISPR screening technology,computational methods,and THPA database as experimental tools for fighting cancer.We hope that these comments may provide some clues for those engaged in the field of basic and clinical research into iCCA.展开更多
人文社会地理信息系统(geographical information system, GIS)源于人文科学、社会科学和地理信息科学等多个学科的交叉融合,属于自然科学与人文社会科学的学科交叉领域.本文依托南京师范大学长期开展地理信息科学与人文社会科学交叉融...人文社会地理信息系统(geographical information system, GIS)源于人文科学、社会科学和地理信息科学等多个学科的交叉融合,属于自然科学与人文社会科学的学科交叉领域.本文依托南京师范大学长期开展地理信息科学与人文社会科学交叉融合的科研和教学成果,系统分析了人文社会GIS的交叉学科特性,提出了人文社会GIS的内涵和知识体系,设计了“人文社会GIS”课程的创新教学模式,形成了有代表性的学科交叉课程教学实践案例,对于开展“新工科”和“新文科”背景下的交叉学科研究和复合型人才培养具有较好的参考价值.展开更多
气体绝缘金属封闭开关设备(gas insulated metal enclosed switchgear,GIS)机械缺陷是导致设备故障的重要因素,针对单测点、单证据机械缺陷诊断模型信息缺失和精度不足问题,该文提出一种多层融合振动数据分析的GIS设备机械缺陷诊断方法...气体绝缘金属封闭开关设备(gas insulated metal enclosed switchgear,GIS)机械缺陷是导致设备故障的重要因素,针对单测点、单证据机械缺陷诊断模型信息缺失和精度不足问题,该文提出一种多层融合振动数据分析的GIS设备机械缺陷诊断方法。首先,基于真型GIS设备振动模拟平台试验研究测点位置与缺陷类型对振动行为的影响特性;然后,联合统计分析、模态分解、尺度变换方法提出机械振动信号整体与局部信息关注的复合参数分析方法,引入主成分分析开展多测点振动信息的特征层融合降维;最后,提出改进放缩权重的Dempster-Shafer(DS)证据理论和Bagging投票机制的强/弱基学习器决策层融合机制,联合构建多层融合振动数据分析的GIS设备机械缺陷诊断模型。结果表明:不同类型机械缺陷信号的响应幅值、特征频点和畸变程度存在显著差异,复合特征参量大小及分散程度各不相同;同时,测点位置对缺陷信号的复合振动特征参量的表现形式及分布区间也具有一定影响;基于多层融合数据分析的诊断模型实现缺陷有效识别,辨识准确率为98.66%,相比单一分类器诊断效果提升5.83%。该文可为GIS设备机械缺陷诊断方法提供有价值的参考。展开更多
基金Supported by The 2021 Central-Guided Local Science and Technology Development FundLanzhou COVID-19 Prevention and Control Technology Research Project,No.2020-XG-1Gansu Province Outstanding Graduate Student"Innovation Star"Project,No.2022CXZX-748,No.2022CXZX-746.
文摘BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer.In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.METHODS Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)database.Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases.Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients.The correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also analyzed.Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)genes.The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was performed.The study also validated the level of mRNA or protein expression of PDHB in several cancers.Finally,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver cancer.RESULTS PDHB was significantly and differently expressed in most cancers.PDHB was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinoma,and brain lower grade glioma.In some cancers,PDHB expression was clearly associated with gene mutations,clinicopathological stages,and expression of TMB,MSI,and ICP genes.The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment.In addition,single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells.This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation,migration,and invasion functions of hepatoma cells.CONCLUSION As a member of pan-cancer,PDHB may be a novel cancer marker with potential value in diagnosing cancer,predicting prognosis,and in targeted therapy.
文摘BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.
基金Supported by The National Key Research and Development Program of China,No.2017YFC1308602The Research Funds by the Fifth Affiliated Hospital of Harbin Medical University,No.2022-002 and No.2023-001.
文摘In this editorial we comment on the article by Tang et al published in the recent issue of World Journal of Hepatology.Drug therapy of intrahepatic cholangiocarcinoma(iCCA)poses an enormous challenge since only a small proportion of patients demonstrate beneficial responses to therapeutic agents.Thus,there has been a sustained search for novel molecular targets for iCCA.The study by Tang et al evaluated the role of 26S proteasome non-ATPase regulatory subunit 6(PSMD6),a 19S regulatory subunit of the proteasome,in human iCCA cells and specimens.The authors employed clustered regularly interspaced short palindromic repeat(CRISPR)knockout screening technology integrated with the computational CERES algorithm,and analyzed the human protein atlas(THPA)database and tissue microarrays.The results show that PSMD6 is a gene essential for the proliferation of 17 iCCA cell lines,and PSMD6 protein was overexpressed in iCCA tissues without a significant correlation with the clinicopathological parameters.The authors conclude that PSMD6 may play a promoting role in iCCA.The major limitations and defects of this study are the lack of detailed information of CRISPR knockout screening,in vivo experiments,and a discussion of plausible mechanistic cues,which,therefore,dampen the significance of the results.Further studies are required to verify PSMD6 as a molecular target for developing novel therapeutics for iCCA.In addition,the editorial article summarizes the latest advances in molecular targeted drugs and recently emerging immunotherapy in the clinical management of iCCA,development of proteasome inhibitors for cancer therapy,and advantages of CRISPR screening technology,computational methods,and THPA database as experimental tools for fighting cancer.We hope that these comments may provide some clues for those engaged in the field of basic and clinical research into iCCA.
文摘人文社会地理信息系统(geographical information system, GIS)源于人文科学、社会科学和地理信息科学等多个学科的交叉融合,属于自然科学与人文社会科学的学科交叉领域.本文依托南京师范大学长期开展地理信息科学与人文社会科学交叉融合的科研和教学成果,系统分析了人文社会GIS的交叉学科特性,提出了人文社会GIS的内涵和知识体系,设计了“人文社会GIS”课程的创新教学模式,形成了有代表性的学科交叉课程教学实践案例,对于开展“新工科”和“新文科”背景下的交叉学科研究和复合型人才培养具有较好的参考价值.
文摘气体绝缘金属封闭开关设备(gas insulated metal enclosed switchgear,GIS)机械缺陷是导致设备故障的重要因素,针对单测点、单证据机械缺陷诊断模型信息缺失和精度不足问题,该文提出一种多层融合振动数据分析的GIS设备机械缺陷诊断方法。首先,基于真型GIS设备振动模拟平台试验研究测点位置与缺陷类型对振动行为的影响特性;然后,联合统计分析、模态分解、尺度变换方法提出机械振动信号整体与局部信息关注的复合参数分析方法,引入主成分分析开展多测点振动信息的特征层融合降维;最后,提出改进放缩权重的Dempster-Shafer(DS)证据理论和Bagging投票机制的强/弱基学习器决策层融合机制,联合构建多层融合振动数据分析的GIS设备机械缺陷诊断模型。结果表明:不同类型机械缺陷信号的响应幅值、特征频点和畸变程度存在显著差异,复合特征参量大小及分散程度各不相同;同时,测点位置对缺陷信号的复合振动特征参量的表现形式及分布区间也具有一定影响;基于多层融合数据分析的诊断模型实现缺陷有效识别,辨识准确率为98.66%,相比单一分类器诊断效果提升5.83%。该文可为GIS设备机械缺陷诊断方法提供有价值的参考。